Although the groups A, C, Y and W135 capsular polysaccharides of N. meningitidis have been used with some success in providing homologous serogroup immunity in humans, the group B polysaccharide is only poorly immunogenic.
The poor immunogenicity of the group B meningococcal polysaccharide (GBMP) and the structurally identical E. coli KI capsular polysaccharide (1, 2, 3) preclude their use as vaccines against meningitis caused by group B meningococcal (GBM) and E. coli KI organisms. Although GBM organisms are able to produce low levels of GBMP-specific antibodies in animals and humans, these antibodies are, with one notable exception, almost exclusively IgM and of relatively low affinity (4). Recently Frosch et al. (5) reported that GBMP-specific monoclonal antibodies of the IgG isotype could be readily produced by injecting a specialized strain of autoimmune NZB mice with GBM organisms. The poor immunogenicity of these polysaccharides is probably attributable to tolerance due to cross-reactive tissue components because of the identification of structurally similar .alpha.-(2.fwdarw.8)-linked oligomers of sialic acid in the gangliosides of human and animal fetal brain tissue (6,7). This structural mimicry probably also accounts for the importance of these capsular polysaccharides as virulence factors in the GBM and E. coli KI organisms (3). Because of the poor immunogenicity of the GBMP, other strategies to produce a GBM vaccine have been explored, including the use of serotype protein antigens alone (8) and in combination (9, 10) with the GBMP, and the use of serotype lipooligosaccharides conjugated to protein carriers (11).
Chemical manipulation of the GBMP has been tried in which it was covalently coupled to tetanus toxoid (2). However, this type of conjugation failed to enhance the immunogenicity of the GBMP to the desired degree (2, and vide infra).
Improvement in the immune response by structural modification within the GBM polysaccharide apparently has not been attempted so far and this invention is an initial development in this direction. It would be desirable to further chemically modify the GBM polysaccharide prior to its conjugation in such a way as to make significant structural changes in it, while still being able to retain its antigenicity to group GBM polysaccharide-specific antibodies. Thus the modified polysaccharide-conjugate could conceivably elicit more cross-reactive antibodies to the native GBM polysaccharide than the native GBM polysaccharide-conjugate itself.